Prior to the present invention it was generally believed that serine protease inhibitors could be used only to supplement a deficiency occurring as a result of a genetic defect or a chemically produced deficiency resulting from an event such as smoking. Moreover, no consideration was previously given for directly controlling diseases in which mast cells are implicated by administering serine protease inhibitors when serum levels of proteases or protease inhibitors are normal. Mast cells have been found to be implicated in diseases and events such as allergic and non-allergic rhinitis, nasal polyposis, atopic dermatitis, including psoriasis, contact dermatitis, pancreatitis, emphysema, asthma, colitis, Crohn's Disease, wound healing, cluster headaches, coronary artery spasm, etc.
The role of mast cells in humans is the same as in animals. addition, animals contain counterparts to human .alpha.-1-antichymotrypsin, .alpha.-1-antitrypsin, and other serine protease inhibitors. In fact, it has been shown that human .alpha.-1-antitrypsin will bind with animal mast cells and the mediators derived therefrom.
Inflammation is a non-specific response of tissues to diverse stimuli or insults and results in release of a variety of materials at the site of inflammation that induce pain. It is now recognized that mast cells are implicated in the pathophysiology of inflammatory skin conditions as well as in other physiological disorders. Mast cells provide the greatest source of histamines in acute inflammation. Basophils are another source. Mast cells have also been noted in hypertrophic scars.
Eosinophils, basophils and neutrophils are prominent in inflammatory lesions due to the potent chemoattractants released. Neutrophils are a main source of serine elastase and cathepsin G which are important in the tissue damage resulting from inflammation.
Kallikreins and kinins are recognized as being associated with defense and repair responses in mammals. However, excess kallikreins and kinins can cause pain and tissue damage.
The most direct approach to therapy of inflammatory skin conditions appears to be a direct attack at the site of inflammation of the mediators of inflammation and pain and the reduction of those neutrophilic derivatives which can cause damage to the growth of new tissue during the healing process.
It is understood that the term "serine protease inhibitors" as used herein refers to the inhibitors derived from a human source and the corresponding recombinant product which is either glycosylated or non-glycosylated.